Colorectal CancerPhase 2NCT00466505
Cetuximab & Celecoxib for Metastatic Colorectal Cancer or Colorectal Cancer That Cannot Be Removed by Surgery
A Phase 2 study testing cetuximab, celecoxib and proteomic profiling in people with Colorectal Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- cetuximab, celecoxib and proteomic profiling
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Nov 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > or equal to 20 mm with conventional techniques or as > or equal 10 mm with spiral CT scan.
- Patients must have progressed after at least 1 chemotherapy regimen for advanced disease. No prior therapy which specifically and directly targets the EGFR pathway.
- Age 18 years or older
- ECOG performance status ≤ 2.
- Life expectancy of greater than 3 months.
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- Normal organ and marrow functions as defined below:
- absolute neutrophil count ≤ 1,500/μl
- platelets ≤ 100,000/μl
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) > or equal to 2.5 times institutional upper limit of normal or > or equal to 5.0 times normal if liver metastases are present
- creatinine within normal institutional limits OR
- creatinine clearance > or equal to 60 mL/min/1.73 m2 for patients creatinine levels above institutional normal
- The effects of cetuximab and/or celecoxib on the developing human fetus at the recommended therapeutic doses are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to provide written informed consent.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Prior severe infusion reaction to a monoclonal antibody
- Serum calcium >12.0 mg/dl.
- Patients must be off all other selective or non-selective COX-2 inhibitors for at least 2 weeks prior to study entry (with the exception of 81 mg of daily aspirin).
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- No major surgery within 4 weeks. No minor surgery (laparoscopy, thoracoscopy, port placement) within 1 week.
- Patients must be > 4 weeks from prior pelvic radiation and recovered from side effects.
- Patients must be > 1 week from prior palliative radiation and have recovered from all side effects.
- Prior treatment with EGFR targeting therapies.
- Significant traumatic injury occurring within 28 days prior to treatment.
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because cetuximab is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab, breastfeeding should be discontinued if the mother is treated with cetuximab.
- Patients with known HIV disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: A Phase 2 Study of Cetuximab in Combination With Celecoxib in Colorectal Cancer
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab together with celecoxib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with celecoxib works in treating patients with metastatic colorectal cancer or colorectal cancer that cannot be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- Determine the time to progression in patients with unresectable or metastatic colorectal cancer treated with cetuximab and celecoxib.
Secondary
- Determine the response rate, median survival, and 1-year survival rate of patients treated with this regimen.
- Determine the toxicity profile of this regimen in these patients.
- Determine the feasibility of testing urinary PGE-M in patients treated with this regimen.
- Determine the feasibility of testing serum transforming growth factor-α and amphiregulin in patients treated with this regimen.
- Determine the effects of this regimen on the EGFR pathway in tumor cells (i.e., phosphorylated EGFr, phosphorylated AKT, activated mitogen-activated protein kinase).
- Determine the effects of this regimen on the cyclooxygenase-2 pathway in tumor cells by measuring PGE-2 levels.
OUTLINE: Patients receive cetuximab IV over 1-2 hours once weekly and oral celecoxib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Serum and urine samples are collected at baseline, after week 1, and every other course thereafter for evaluation of PGE-2 by mass spectrometry, cyclooxygenase-2 activity, and phospho-EGFR levels by western blot analysis and immunohistochemistry. Samples are also analyzed for TGF-α and amphiregulin proteomics.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
- Conditions
- Colorectal Cancer
- Being tested
- cetuximab, celecoxib, proteomic profiling, immunohistochemistry staining method, laboratory biomarker analysis
- Keywords
- recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
Also called Erbitux, IMC-C225
400 mg/m2 iv week 1, then 250 mg/m2 weekly thereafter, starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.
celecoxibDrug
Also called celebrex
200 mg po BID starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.
proteomic profilingGenetic
Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction. We will use LC-MS-MS or MALDITOF mass spectrometry.
immunohistochemistry staining methodOther
phospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections).
laboratory biomarker analysisOther
Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction.
mass spectrometryOther
We will use LC-MS-MS or MALDITOF mass spectrometry. Before any tissues are received, the drug of interest is evaluated via MALDI mass spectrometry on a MDS/Sciex QStar QqTOF mass spectrometer.
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic Intervention | Experimental | Not described Receives: Biological: cetuximab; Drug: celecoxib; Genetic: proteomic profiling; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: mass spectrometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
Number of days from study enrollment to evidence of progressive disease radiographically, with progression defined under RECIST criteria as at least 20% increase in sum of longest diameter of target lesions
Measured: On study date to off study date in this study with median 9.76 months
Secondary outcomes (8)
Patient Response to Treatment
Number of patients in each response category according to RECIST criteria: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Measured: On study date to off study date in this study with median 9.76 months
Overall Survival
Median survival time in months, from on-study date to date of death
Measured: On study date to off study date in this study with median 9.76 months
One Year Survival Rate
Percent of patients who remain alive one year from on-study date
Measured: 1 year from on-study date
Number of Patients With Each Worst-grade Toxicity Response
Number of patients with worst-grade toxicity response of each grade (grade 1 to 5) following NCI Common Toxicity Criteria, with grade 1=mild adverse event; 2=moderate adverse event; 3=severe and undesirable adverse event; 4=life-threatening or disabling adverse event; 5=death.
Measured: On study date to off study date in this study with median 9.76 months
Urinary PGE-M : Treatment Cycle 1
Measurement in ng/mL of a stable metabolite of prostaglandin E2 (PGE-M) in urine during treatment cycle 1
Measured: on-study week 5
Serum TGF-alpha: Treatment Cycle 1
Measurement in ng/mL of tumor growth factor-alpha (TGF-alpha) in serum samples during treatment cycle 1
Measured: on-study week 5
Urinary PGE-M : Treatment Cycle 2
Measurement in ng/mL of a stable metabolite of prostaglandin E2 (PGE-M) in urine during treatment cycle 2
Measured: on-study week 9
Serum TGF-alpha: Treatment Cycle 2
Measurement in ng/mL of tumor growth factor-alpha (TGF-alpha) in serum samples during treatment cycle 2
Measured: on-study week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startMay 2005
- Primary completionJul 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jordan Berlin, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Jordan D. Berlin, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466505
- Sponsor's protocol ID
- VICC GI 0410
- Other IDs
- P30CA068485, VU-VICC-GI-0410, VU-IRB-040227
- Status last verified
- Dec 2012
- First submitted
- 25 Apr 2007
- Last updated
- 19 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Cetuximab in Combination With Celecoxib in Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00466505
- Acronym / sponsor ID
- VICC GI 0410
- Conditions
- Colorectal Cancer
- Keywords
- recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 27 Apr 2007 (estimated)
- Results
- Posted 16 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab together with celecoxib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with celecoxib works in treating patients with metastatic colorectal cancer or colorectal cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- Determine the time to progression in patients with unresectable or metastatic colorectal cancer treated with cetuximab and celecoxib.
Secondary
- Determine the response rate, median survival, and 1-year survival rate of patients treated with this regimen.
- Determine the toxicity profile of this regimen in these patients.
- Determine the feasibility of testing urinary PGE-M in patients treated with this regimen.
- Determine the feasibility of testing serum transforming growth factor-α and amphiregulin in patients treated with this regimen.
- Determine the effects of this regimen on the EGFR pathway in tumor cells (i.e., phosphorylated EGFr, phosphorylated AKT, activated mitogen-activated protein kinase).
- Determine the effects of this regimen on the cyclooxygenase-2 pathway in tumor cells by measuring PGE-2 levels.
OUTLINE: Patients receive cetuximab IV over 1-2 hours once weekly and oral celecoxib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Serum and urine samples are collected at baseline, after week 1, and every other course thereafter for evaluation of PGE-2 by mass spectrometry, cyclooxygenase-2 activity, and phospho-EGFR levels by western blot analysis and immunohistochemistry. Samples are also analyzed for TGF-α and amphiregulin proteomics.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Therapeutic Intervention | Experimental | Biological: cetuximab, Drug: celecoxib, Genetic: proteomic profiling, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis, Other: mass spectrometry |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > or equal to 20 mm with conventional techniques or as > or equal 10 mm with spiral CT scan.
- Patients must have progressed after at least 1 chemotherapy regimen for advanced disease. No prior therapy which specifically and directly targets the EGFR pathway.
- Age 18 years or older
- ECOG performance status ≤ 2.
Key exclusion criteria (15 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Prior severe infusion reaction to a monoclonal antibody
- Serum calcium >12.0 mg/dl.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximabAlso: Erbitux, IMC-C225400 mg/m2 iv week 1, then 250 mg/m2 weekly thereafter, starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol. | Biological | Therapeutic Intervention |
| celecoxibAlso: celebrex200 mg po BID starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol. | Drug | Therapeutic Intervention |
| proteomic profilingSerum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction. We will use LC-MS-MS or MALDITOF mass spectrometry. | Genetic | Therapeutic Intervention |
| immunohistochemistry staining methodphospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections). | Other | Therapeutic Intervention |
| laboratory biomarker analysisSerum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction. | Other | Therapeutic Intervention |
| mass spectrometryWe will use LC-MS-MS or MALDITOF mass spectrometry. Before any tissues are received, the drug of interest is evaluated via MALDI mass spectrometry on a MDS/Sciex QStar QqTOF mass spectrometer. | Other | Therapeutic Intervention |
Primary outcome
Progression-free Survival (PFS)
Time frame: On study date to off study date in this study with median 9.76 months
Number of days from study enrollment to evidence of progressive disease radiographically, with progression defined under RECIST criteria as at least 20% increase in sum of longest diameter of target lesions
8 secondary outcomes
Patient Response to Treatment
Time frame: On study date to off study date in this study with median 9.76 months
Overall Survival
Time frame: On study date to off study date in this study with median 9.76 months
One Year Survival Rate
Time frame: 1 year from on-study date
Number of Patients With Each Worst-grade Toxicity Response
Time frame: On study date to off study date in this study with median 9.76 months
Urinary PGE-M : Treatment Cycle 1
Time frame: on-study week 5
Serum TGF-alpha: Treatment Cycle 1
Time frame: on-study week 5
Urinary PGE-M : Treatment Cycle 2
Time frame: on-study week 9
Serum TGF-alpha: Treatment Cycle 2
Time frame: on-study week 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordan D. Berlin, MD principal investigator
Vanderbilt-Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab, celecoxib and proteomic profiling in people with Colorectal Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: On study date to off study date in this study with median 9.76 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2012.